Ocinaplon: Difference between revisions

{{short description|Chemical compound}}

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'''Ocinaplon''' is an [[anxiolytic]] drug in the [[pyrazolopyrimidine]] family of drugs. Other pyrazolopyrimidine drugs include [[zaleplon]] and [[indiplon]].

Ocinaplon has a similar pharmacological profile to the [[benzodiazepine]] family of drugs, but with mainly anxiolytic properties and relatively little [[sedative]] or [[amnestic]] effect.<ref>{{cite journal | vauthors = Lippa A, Czobor P, Stark J, Beer B, Kostakis E, Gravielle M, Bandyopadhyay S, Russek SJ, Gibbs TT, Farb DH, Skolnick P | display-authors = 6 | title = Selective anxiolysis produced by ocinaplon, a GABA(A) receptor modulator | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 20 | pages = 7380–5 | date = May 2005 | pmid = 15870187 | pmc = 1129138 | doi = 10.1073/pnas.0502579102 | bibcode = 2005PNAS..102.7380L | doi-access = free }}</ref>

==Medical uses==

A 2019 review found tentative evidence of benefit in anxiety.<ref>{{cite journal | vauthors = Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N | title = Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis | journal = Lancet | volume = 393 | issue = 10173 | pages = 768–777 | date = February 2019 | pmid = 30712879 | doi = 10.1016/S0140-6736(18)31793-8 | s2cid = 72332967 }}</ref>

The mechanism of action by which ocinaplon produces its anxiolytic effects is by modulating [[GABAA receptor|GABA_A]] receptors,<ref>{{cite journal | vauthors = Mirza NR, Rodgers RJ, Mathiasen LS | title = Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 316 | issue = 3 | pages = 1291–9 | date = March 2006 | pmid = 16339395 | doi = 10.1124/jpet.105.094003 | s2cid = 21913400 }}</ref> although ocinaplon is more subtype-selective than most benzodiazepines.<ref>{{cite journal | vauthors = Atack JR | title = The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics | journal = Expert Opinion on Investigational Drugs | volume = 14 | issue = 5 | pages = 601–18 | date = May 2005 | pmid = 15926867 | doi = 10.1517/13543784.14.5.601 | s2cid = 22793644 }}</ref>

Development of ocinaplon is discontinued due to liver complications that occurred in one of the Phase III subjects.<ref>{{cite web | title = DOV Pharmaceutical, Inc. Places Ocinaplon Phase III Clinical Trial On Hold | url = http://www.prnewswire.com/news-releases/dov-pharmaceutical-inc-places-ocinaplon-phase-iii-clinical-trial-on-hold-55011422.html | archive-url = https://web.archive.org/web/20160304042155/http://www.prnewswire.com/news-releases/dov-pharmaceutical-inc-places-ocinaplon-phase-iii-clinical-trial-on-hold-55011422.html | archive-date = 4 March 2016 | work = PR NewsWire }}</ref>

==Synthesis==

[[File:Ocinaplon synthesis.svg|thumb|center|500px|Ocinaplon synthesis: {{US patent|4521422}} Further reading:<ref>{{cite journal | vauthors = Baumann M, Baxendale IR | title = An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles | journal = Beilstein Journal of Organic Chemistry | volume = 9 | pages = 2265–319 | date = October 2013 | pmid = 24204439 | pmc = 3817479 | doi = 10.3762/bjoc.9.265 }}</ref><ref>[http://www.arkat-usa.org/get-file/34069/ ARKIVOC 2010 (ii) 267-282]</ref>]]

Condensation of [[4-Acetylpyridine]]<ref>{{cite journal | vauthors = LaMattina JL, Sulesk RT |doi=10.15227/orgsyn.064.0019|title=A-Amino Acetals: 2,2-Diethoxy-2-(4-Pyridyl)Ethylamine|journal=Organic Syntheses|volume=64|pages=19|year=1986}}</ref> with N,N-Dimethylformamide dimethyl acetal ([[DMFDMA]]) gives the "enamide" ('''3'''). This is then condensed with (3-Amino-1H-pyrazol-4-yl)(2-pyridinyl)methanone ('''4''') (96219-90-8).<ref>{{US patent|4900836}}</ref><ref>{{Cite patent|country=CA|number=1243029}}</ref> This is the same intermediate as was used in the synthesis of [[zaleplon]] in which the nitrile is replaced by a 2-acetylpyridil moiety. This affords the [[anxiolytic]] agent ocinaplon ('''5''').

== References ==

{{reflist}}

{{GABAAR PAMs}}

[[Category:Hepatotoxins]]

[[Category:GABAA receptor positive allosteric modulators]]